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Development of Cancer Immunotherapy Utilizing Novel Activation Mechanism of gamma-delta T Cells by 4th Generation Bisphosphonates

Research Project

Project/Area Number 18K07274
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 50020:Tumor diagnostics and therapeutics-related
Research InstitutionTokyo Women's Medical University

Principal Investigator

KOBAYASHI Hirohito  東京女子医科大学, 医学部, 准教授 (80318047)

Project Period (FY) 2018-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Keywords癌性腹膜炎 / ガンマデルタ型T細胞 / 活性化法 / 腎細胞がん / 卵巣がん / 癌免疫細胞療法 / ガンマ・デルタ型T細胞 / ベータリン酸カルシウム / マクロファージ / 癌性腹水 / 第4世代ビスホスホン酸 / がん免疫細胞療法 / 腹水濾過濃縮 / 第4世代ビスホスホン酸
Outline of Final Research Achievements

The treatment of refractory ascites due to carcinomatous peritonitis can be alleviated through the use of CART. During the filtration of ascitic fluid in this procedure, gamma delta (γδ) T cells are among the cellular components removed. Research has developed a cell therapy product for cancer immunotherapy by culturing these γδ T cells. When comparing the traditional method using 2M3B-1PP for culturing these cells, the new method employs Tetrakis-pivaloyloxymethyl-2-(thiazole-2-ylamino)ethylidene-1,1-bisphosphonate. This new approach has shown to reduce the contamination of cancer cells and can increase the γδ T cell yield by up to 77 times. Moreover, the cultured γδ T cells maintained their cytotoxic activity even within autologous ascites. The study suggests that intraperitoneal administration of these cultured γδ T cells could be a beneficial therapeutic approach.

Academic Significance and Societal Importance of the Research Achievements

癌性腹膜炎による難治性腹水は、患者のQOLを著しく低下させる。症状緩和に腹水濾過濃縮再静注法が用いられるが、効果は一時的であり複数回の腹腔穿刺が必要である。本研究は本来破棄される細胞成分を用いて癌免疫細胞療法に用いる細胞製剤の開発にある。抗腫瘍活性を有する腹水由来のガンマ・デルタ型T細胞製剤を患者腹腔内へ投与することで難治性腹水の新たな治療戦略となる。また、原料採取に際し新たな患者負担は生じることはなく、持続可能な免疫療法となる。

Report

(7 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (2 results)

All 2023 2019

All Journal Article (2 results) (of which Peer Reviewed: 1 results)

  • [Journal Article] A retrospective cohort study of the impact of peripheral blood gamma- delta T cells to prognosis of nonmetastatic renal cell cancer after curative resection2023

    • Author(s)
      Kobayashi Hirohito、Kondo Tsunenori、Iizuka Junpei、Yoshida Kazuhiko、Takagi Toshio
    • Journal Title

      Urologic Oncology: Seminars and Original Investigations

      Volume: 41 Issue: 12 Pages: 488.e1-488.e9

    • DOI

      10.1016/j.urolonc.2023.10.001

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 癌性腹水から効率良くガンマ・デルタ型T細胞を誘導する方法の基礎的検討2019

    • Author(s)
      小林博人、張奇、阿部結貴、田端務、菅野仁
    • Journal Title

      東京女子医医科大学総合研究所紀要

      Volume: 39 Pages: 76-77

    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2025-01-30  

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